Neuropilin-1 (NRP1) is a multi-functional receptor that contributes to the development of the nervous and vascular systems. NRP1 was initially described as a receptor that binds the semaphorin 3A ligand, acting with plexin co-receptors to regulate axon guidance (He and Tessier-Lavigne, Cell (1997) 90:739-51). It was later shown that NRP1 also binds members of the vascular endothelial growth factor (VEGF) ligand family to mediate vascular development (Soker et al., Cell (1998) 92:735-45; Kawasaki et al., Development (1999) 126:4895-902). In addition, several studies have proposed a role for NRP1 in tumor biology by regulating vascular and/or tumor cell functions (Bielenberg et al., Exp Cell Res (2006) 312:584-93).
Pan et al., J Biol Chem (2007) 282:24049-56 showed that a monoclonal antibody that binds to NRP1 reduced VEGF-mediated endothelial cell migration in vitro (see also PCT Publication No. WO2007/056470). Blocking VEGF interaction with NRP1 in vivo reduced angiogenesis and vascular remodeling. The anti-NRP1 antibody slowed tumor growth as a single agent; it is proposed that this is due to anti-NRP1 antibody-mediated reduction of vessel sprouting through a VEGF-dependent process. The anti-NRP1 antibody enhanced the anti-angiogenic and anti-tumor effects of VEGF blockade with an anti-VEGF antibody. The data suggest that by reducing vascular remodeling with anti-NRP1, vessels are likely to retain a more immature phenotype. As immature vessels are believed to be more VEGF-dependent, blood vessels in anti-NRP1-treated tumors may be rendered more susceptible to anti-VEGF therapy, thus resulting in combination efficacy in tumor models when combining both therapies (Pan et al., Cancer Cell (2007) 11:53-67). Given the role of NRP1 in angiogenesis, additional tools to detect the presence of NRP1 are desirable.